For Research Use Only

 

Summary:

The Notch signaling is essential for appropriate cell differentiation and cell fate decisions. DLL1 is a human homolog of the Drosophila Notch ligand Delta. A cDNA encoding DLL1 was isolated by a PCR cloning approach utilizing a primer pair whose sequences were derived from the Delta gene. DLL1 is the 723- amino acid type I transmembrane protein, which is 88% identical to the mouse Dll1 protein, having a DSL domain followed by 8 tandem EGF-like repeats and a short cytoplasmic C-terminal region. Engagement of Notch with DLL1 was shown to inhibit the differentiation of muscle, myeloid, or lymphoid progenitors. It has been shown that DLL1 is subjected to ADAM metaloproteases (ADAM10 & ADAM12) and presenilin-dependent intramembranous gamma-secretase processing, resulting in the production of soluble extracellular domain and intracellular domain. ADAM-mediated shedding of DLL1 in a subset of cells during myogenic differentiation in vitro seems to contribute to downregulation of Notch signaling in neighboring cells and facilitates their progression into differentiation such that the proteolytic processing of DLL1 helps achieve an asymmetry in Notch signaling in initially equivalent myogenic cells and helps sustain the balance between differentiation and self-renewal. Since obesity is a consequence of increase in adipocyte proliferation, DLL1 could be also involved in differentiation and self-renewal of adipocyte stem cells. Depending on metabolic status, shedding of DLL1 could be affected. Thus, measurement of soluble DLL1 in serum or plasma likely provides a novel indication of disease status in metabolic dysfunctions.